Pineal Research Articles

Melatonin modulates TLR4/MyD88/NF-κB signaling pathway to ameliorate cognitive impairment in sleep-deprived rats.

Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1β, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aβ42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.

Overlapping action of melatonin and female reproductive hormones-Understand the impact in pregnancy and menopause.

Melatonin is an indolamine secreted to circulation by the pineal gland according to a circadian rhythm. Melatonin levels are higher during nighttime, and the principal function of this hormone is to organize the temporal night and day distribution of physiological adaptive processes. Besides hormonal pineal production, melatonin is synthesized in various organs and tissues like the ovaries or the placenta for local utilization. In addition to its function as a circadian messenger, melatonin is also associated with many physiological functions. For example, melatonin has antioxidant properties and is involved in the regulation of energy and bone metabolism, and reproduction. Melatonin impacts several stages of reproduction and the action across the hypothalamus-pituitary-gonadal axis is well described. However, it is not well understood how those actions impact the female reproductive hormones secretion nor the consequent physiological outcomes. Thus, the first part of this chapter describes the regulation of female reproductive hormone synthesis by melatonin. Moreover, melatonin and female reproductive hormones have coincident physiological functions. Life stages like pregnancy or menopause are characterized by alterations in the reproductive hormones secretion that may be associated with certain physiological stages. Therefore, the second part discusses whether melatonin fluctuations could have an overlapping role with reproductive hormones in contributing to clinical outcomes associated with pregnancy and menopause.

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT.

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT). Ehrlich ascites carcinoma (EAC) cells were administered into the mice by subcutaneous injection. Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days. Volumetric measurements for the taken tumors were made with micro-CT imaging, immunohistochemistry (IHC), real-time polymerase chain reaction (PCR) and AgNOR. Statistically, the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images. In the IHC analysis, the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8 (F8) expression were compared with the control group. It was determined that there was a significant decrease (p < 0.05). Significant differences were found in the total AgNOR area/nuclear area (TAA/NA) ratio in the treatment groups (p < 0.05). Furthermore, there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase (PI3K), AKT Serine/Threonine Kinase (PKB/AKT) genes (p < 0.05). Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin; It was observed that 100 µg/mL melatonin dose caused an increase in the apoptotic cell death. In this study, we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models. Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.

Comparison of the efficacy of royal jelly and melatonin combinations in experimentally induced wounds in geriatric and young mice.

Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Melatonin, a circadian indoleamine, is produced in the pineal gland and other organs. This study explores the effects of melatonin and royal jelly, both individually and combined, on wound healing in geriatric and young mice. The study includes 90 Balb/C mice divided into ten groups to assess the effects of royal jelly and melatonin on wound healing. Royal jelly was applied topically at a concentration of 300 mg/kg. Melatonin was formulated in a vaseline-based pomade at a concentration of 5 mg/kg. The substances were applied either separately or in combination to wounds created on the mice. Both substances significantly enhanced wound healing at a macroscopic level in both age groups. Melatonin was found to be more effective during the initial wound formation process, whereas royal jelly was more beneficial during the granulation phase. However, significant results at a histopathological level were observed only in geriatric animals. The findings suggest a potential new therapeutic approach to enhance wound healing, particularly in elderly individuals. However, these findings need to be supported through further research and clinical trials.

Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti-signalling protein (asip1) overexpression in zebrafish.

Temporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.

Exoscope-based supracerebellar infratentorial approach for a pineal meningioma in the prone position.

The supracerebellar infratentorial (SCIT) approach is a well-described corridor to lesions in the quadrigeminal cistern, pineal gland, and dorsal midbrain. It can be performed in the prone or sitting position. The sitting position offers the benefit of gravity retraction of the cerebellum but comes at the expense of nonergonomic hand positioning and the potential risk of air embolism. The 3D exoscope is an alternative to the operating microscope and permits the SCIT approach in the prone position with excellent visualization. This video demonstrates exoscope-based SCIT approach for resection of a pineal meningioma in the prone position. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23155.

Blockage of CSF Outflow in Rats after Deep Cervical Lymph Node Ligation Observed Using Gd-based MR Imaging.

To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI. Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF_C1), CSF between the olfactory bulbs (CSF_OB), CSF at the pituitary recess (CSF_PitR), and CSF at the pineal recess (CSF_PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared. Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF_C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF_OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF_PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021). The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.

The association between melatonin hormone and reproductive hormones in polycystic ovary syndrome: A case–control study

Abstract Background: One of the common endocrine disorders is polycystic ovary syndrome (PCOS) with prevalence of about 5%–15% of women within reproductive age. It is related to androgen disturbance, obesity, and irregular menstrual cycle. Pineal gland secretes melatonin hormone, which is involved in the regulation of the circadian rhythm. Melatonin receptors in the ovary adjust sex steroid secretion. Furthermore, it is considered a strong antioxidant, which protects ovarian follicles during follicular maturation. Objectives: To evaluate the level of melatonin in patients with PCOS and its relation with reproductive hormones and anthropometric measures. Materials and Methods: A case-control study included 200 women in reproductive age (20–40 years), including 100 PCOS patients and 100 controls who appeared to be in generally good health. Anthropometric measurements were evaluated. Reproductive hormones and anti-Müllerian hormone (AMH) were evaluated using the mini VIDAS method. Human MT (Melatonin) ELISA Kit from Elabscience source (USA) was used for measuring melatonin levels. Results: Luteinizing hormone/follicle-stimulating hormone (FSH) ratio, AMH, and melatonin were significantly higher in PCOS women, whereas FSH level was significantly lower in PCOS compared with controls. There was an adverse relationship between melatonin levels with thigh circumference, waist circumference, and waist/hip ratio (P &lt; 0.05). There was a significant adverse correlation between melatonin and testosterone hormone in PCOS patients (P &lt; 0.05). Melatonin level showed an AUC of 0.755 at a cutoff point of 20 ng/mL and more, giving a sensitivity (78%) and specificity (75%). Conclusions: Although PCOS women had higher serum melatonin concentrations, their effect on ovarian hormones is diminished. Melatonin had a connection with androgen, and melatonin supplements may improve metabolic dysfunction in PCOS patients.

Occipital-interhemispheric transtentorial pineal mass resection.

The occipital approach for pineal tumors was first described by James Poppen in 1966. Since then, it has been widely used for accessing deep-seated tumors as it offers a wider surgical view than the supracerebellar transtentorial approach. This video demonstrates the technical nuances of the occipital transtentorial approach and the exoscopic dissection of a pineal gland tumor in a 66-year-old male. Use of the exoscope over the microscope provides certain ergonomic advantages and improves surgical workflow, as demonstrated here. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23161.

Pinealoma Masquerading as Post-Epidural Spinal Injection Dural Tear/Side Effect in a Patient with Chronic Back Pain

Introduction: Pineal gland neoplasms are uncommon, accounting for less than 1% of adult brain tumors. The variable morphology, radiological characteristics, and symptomatic manifestations further complicate the prompt diagnosis and management [1]. Symptoms commonly arise from the tumor’s mass effect with compression of surrounding structures (e.g., headaches, nausea, vomiting, blurry vision, vertigo, fatigue) and may further induce obstructive hydrocephalus and Parinaud’s syndrome [2]. However, with Non-Specific or atypical pinealoma presentation, overlapping medical history suggestive of alternative etiologies may obscure the underlying diagnosis and delay appropriate workup and treatment. Case Presentation: We present a 41-year-old man with a history of chronic lower back pain and lumbar disc herniation presenting with worsening fatigue, cognitive lapses, and gait issues for three to four weeks, as well as nausea, vomiting, and blurry vision for the last three days. One month ago, the patient underwent bilateral L5-S1 transforaminal epidural steroid injection for lumbar radiculopathy and discogenic pain, which resolved the pain. Presentation appeared consistent with dural tear secondary to recent epidural injection. Brain imaging was obtained in the setting of altered mental status and neurologic symptoms. MRI showed a 17mm enhancing pineal mass with associated supratentorial obstructive hydrocephalus, with grade 1 papilledema found on ophthalmologic exam. CT chest/abdomen/pelvis was negative for primary lesions. Six days after initial presentation, the patient underwent an endoscopic third ventriculostomy for pineal tumor biopsy, and CSF collection for hydrocephalus treatment. The patient tolerated the procedure well without complications, was deemed medically and neurologically stable, and was discharged two days post-operatively. He continued to have lapses in judgment, fatigue, and double vision, and underwent a full craniotomy three weeks after discharge, which revealed a vermis lesion. Pathological report revealed a high-grade glioma. Conclusion: Unintentional dural tears occur in 1-3% of epidural spinal injections, commonly presenting as headaches, nausea, vomiting, and dizziness/ataxia [3]. However, this case highlights the need for clinical suspicion of alternative causes for similar presentation and the utility of further workup.

Связь кисты эпифиза с особенностями строения головного мозга и наличием определенных черт личности

Aim. To study the psychological characteristics and microstructural changes of the brain, according to magnetic resonance imaging (MRI), in healthy volunteers with pineal cyst to determine their clinical significance. Design. A prospective case — control study. Materials and methods. The study involved conditionally healthy volunteers. Based on brain MRI data, study groups were formed: the main group consisted of 33 people with pineal cyst, the control group consisted of 30 people with normal epiphysis structure. The groups were comparable in gender and age. We conducted neurological examination, experimental psychological and neuropsychological examinations, MRI of the brain with post-processing of the data obtained by MR Voxel-based morphometry, determination of the level of melatonin in saliva using enzyme immunoassay. Results. The results of experimental psychological and neuropsychological examinations have shown the tendency of people with a pineal cyst to be absorbed in worries, thoughts about something, as well as to express anxiety. According to MR Voxel-based morphometry, it was found that during cystic transformation of the pineal gland, there are zones of increased cortical thickness in both parietal lobes, each of which is located in the central sections of the postcentral gyrus on the left and the superior parietal gyrus on the right. Conclusion. Psychological features in the presence of a pineal cyst indicate the need to include an experimental psychological examination in the protocol of patient management to identify risk groups for affective disorders. The data obtained by us on microstructural changes in the cortex of the parietal lobes during cystic transformation of the epiphysis indicate the variability of the normal structure of the brain substance and require further clarification. Keywords: brain, pineal cyst, anxiety, depression, melatonin, magnetic resonance imaging, magnetic resonance voxel-based morphometry.

Quantitative Anatomical Study of the Supratentorial and Infratentorial “Endoscopic Keyhole” Approach to the Peripineal Region

Background. The pineal region represents significant challenges in terms of neurosurgery. Currently, anatomical research that simulates surgery for the endoscopic keyhole approach to the pineal region is lacking. This study aims to summarize the exposure range and operational characteristics of total endoscopic surgery under the four supratentorial and infratentorial keyhole approaches, through rigorous quantitative anatomical research. We also aim to understand the surgical exposure characteristics and surgical feasibility under each approach. Method. Six wet cadaveric head specimens (a total of 12 sides) were subjected to simulated surgery with a keyhole bone window size of approximately 3 × 4 cm. The median endoscopic supracerebellar infratentorial approach (M‐ESCITA), the paramedian endoscopic supracerebellar infratentorial approach (PM‐ESCITA), the endoscopic occipital transtentorial approach (EOTA), and the endoscopic interhemispheric high occipital transtentorial approach (EHOTA) were used to measure the surgical path depth, maximum distance between the tentorial margins, maximum operable area, operable angle, and relative degree of freedom of each approach. Results. There was no difference in the exposure range of the surgical area. The surgical path of PM‐ESCITA was the longest (p &lt; 0.001), and its horizontal operating angle was the largest (p &lt; 0.001), whereas the anteroposterior operating angle of EHOTA was the largest (p &lt; 0.001). The maximum operational area of M‐ESCITA was the largest in the pineal region (p &lt; 0.01), whereas that of EHOTA was the largest in the tetrapod region (p &lt; 0.001). M‐ESCITA had the highest relative degree of freedom during surgery at the pineal gland level (p &lt; 0.001), PM‐ESCITA at the splenium of the corpus callosum (p &lt; 0.01), and EHOTA at the corpora quadrigemina (p &lt; 0.001). Conclusions. Each of the four endoscopic keyhole approaches has its own advantages. Through anatomical research, doctors can train themselves and master the differences in surgical procedures through different approaches. The choice of approach and surgical challenge are dependent on the microsurgical techniques employed by the surgeon. A balance between minimally invasive and safe endoscopic surgery should be pursued.

Melatonin reduces myocardial cell damage in myocardial ischemia/reperfusion rats by inhibiting NLRP3 activation.

Melatonin (Mel) is an endogenous hormone with many pharmacological effects, such as sedation, hypnosis, antidepressant, blood pressure regulation, anti-inflammatory and anti-tumor. It is mainly synthesized by pineal gland in vivo. Mel can regulate the function of cardiovascular system and effectively reduce myocardial cell injury, thus playing a role in myocardial protection, but its specific mechanism is unclear. Ischemia-reperfusion injury (IRI) often leads to poor prognosis and complications in patients with cardiovascular diseases, and inflammatory reaction mediated by nod-like receptor thermoprotein domain-related protein 3(NLRP3) is an important reason for the further aggravation of subsequent injury after IRI. Rats were intervened with Mel or NLRP3 inhibitor MCC950 for 10 days, and then the IRI rat model was established. After that, rats were anesthetized and killed, and myocardial tissues were collected for experiments. The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Melmay improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibitingNLRP3.

Melatonin facts: Lack of evidence that melatonin is a radical scavenger in living systems.

Melatonin is a small natural compound, so called a neuro-hormone that is synthesized mainly in pineal gland in animals. Its main role is to master the clock of the body, under the surveillance of light. In other words, it transfers the information concerning night and day to the peripheral organs which, without it, could not "know" which part of the circadian rhythm the body is in. Besides its main circadian and circannual rhythms mastering, melatonin is reported to be a radical scavenger and/or an antioxidant. Because radical scavengers are chemical species able to neutralize highly reactive and toxic species such as reactive oxygen species, one would like to transfer this property to living system, despite impossibilities already largely reported in the literature. In the present commentary, we refresh the memory of the readers with this notion of radical scavenger, and review the possible evidence that melatonin could be an in vivo radical scavenger, while we only marginally discuss here the fact that melatonin is a molecular antioxidant, a feature that merits a review on its own. We conclude four things: (i) the evidence that melatonin is a scavenger in acellular systems is overwhelming and could not be doubted; (ii) the transposition of this property in living (animal) systems is (a) theoretically impossible and (b) not proven in any system reported in the literature where most of the time, the delay of the action of melatonin is over several hours, thus signing a probable induction of cellular enzymatic antioxidant defenses; (iii) this last fact needs a confirmation through the discovery of a nuclear factor-a key relay in induction processes-that binds melatonin and is activated by it and (iv) we also gather the very important description of the radical scavenging capacity of melatonin in acellular systems that is now proven and shared by many other double bond-bearing molecules. We finally discussed briefly on the reason-scientific or else-that led this description, and the consequences of this claim, in research, in physiology, in pathology, but most disturbingly in therapeutics where a vast amount of money, hope, and patient bien-être are at stake.

Neuroprotective Potential of Melatonin: Evaluating Therapeutic Efficacy in Alzheimer's and Parkinson's Diseases.

Decreased melatonin levels have been linked to both Alzheimer's disease (AD) and Parkinson's disease (PD), which are the two most prevalent neurodegenerative disorders. The development of sleep disorders is widespread in patients diagnosed with AD or PD. In this regard, calcification of the pineal gland, typically seen in the third decade, has been associated with a reduction in melatonin production. Recent studies have suggested that exogenous melatonin application can be utilized to treat sleep disorders in patients with neurodegenerative diseases. Furthermore, research has shown that deficiencies in melatonin levels in patients with AD or PD begin before a diagnosis of eitherdisease is made. These findings could encourage further research on melatonin as a potential biomarker for the diagnosis or a possible area for the early treatment of these diseases. Many clinical studies have also produced data denoting melatonin treatment as a method to reduce the detrimental neurocognitive effects of these diseases. Further research on the role of melatonin in neurodegenerative diseases could expand symptomatic and prophylactic treatment options for diseases such as AD and PD. This review investigates melatonin's physiological properties, its role in AD and PD, and current findings on its potential therapeutic benefits in AD and PD patients.

Hypothalamic-pituitary-gonadal axis response to photoperiod changes in female guanacos (Lama guanicoe)

The guanaco, a wild South American camelid, is renowned for its remarkable resilience to extreme conditions. Despite this, little is known about how reproductive hormones in female camelids are influenced during their seasonal breeding period, which occurs during long photoperiod. To explore this, the study investigated the response of the hypothalamic-pituitary–gonadal axis in female guanacos during short days (10L:14D; July) and long days (16L:8D; December) in the Mediterranean ecosystem (33°38′28″S, 70°34′27″W). Blood samples from 14 adult animals were collected, and measurements of melatonin, 17β-estradiol, FSH, and LH concentrations were taken. The results showed that melatonin concentration was lower (P < 0.05) during long days than short days, whereas 17β-estradiol, FSH, and LH concentrations were higher (P < 0.05) during long days compared to short days. Furthermore, the study detected the expression of the melatonin receptor 1A and kisspeptin in the hypothalamus and pituitary, suggesting that the pineal gland of female guanacos is sensitive to seasonal changes in day length. These findings also indicate a seasonal variation in the concentration of reproductive hormones, likely linked to the distinct modulation of the hypothalamic-pituitary-gonadal axis of female guanacos during short and long days.

Interaction of Melatonin with Zwitterionic Model Lipid Membranes

Melatonin is a key hormone secreted by the pineal gland in the brain. It interacts strongly with cell membranes and plays a protective role in several diseases such as Alzheimer's disease, cardiovascular diseases, and cancer. Hence, studies on the interaction of melatonin with lipid bilayer membranes have gained importance. In this regard, the present study aims to analyze the influence of different concentrations (0 to 15 mol%) of melatonin on the thermal and structural properties of zwitterionic stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) lipid bilayer model systems by using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The DSC results have shown that melatonin interacts with the membrane in a concentration-dependent fashion, induces patch formation, and alters the phase behaviour by reducing the main phase transition temperature. FTIR data has shown that increasing the melatonin concentration caused a reduction in the wavenumber of C=O and PO$$_{2}^-$$ antisymmetric stretching vibrations corresponding to the ester carbonyl and phosphate groups of SOPC lipids. This indicates the possibility of strong hydrogen bonding of melatonin with the SOPC lipids and nearby water molecules in the environment, suggesting its preferential location near lipid heads at the interfacial region. These results help to understand the organization and interactions of melatonin with membranes and provide insights to develop safe melatonin-based formulations for pharmaceutical applications.

Protective role of melatonin in ultraviolet radiation- induced oxidative stress in human skin photoaging

The ultraviolet radiation of the sun that reaches the earth is made up of ultraviolet A (95%) and ultraviolet B (5%). Exposure to ultraviolet radiation (UVR) is the main factor in photoaging. Chronic exposure to sunlight acts as an environmental stressor, leading to oxidative damage or stress. Oxidative damage stimulates the accumulation of free radicals, such as reactive oxygen species (ROS) or reactive nitrogen species (RNS) that are responsible for premature skin aging. Photoaged skin is characterized externally by irregular pigmentation, wrinkles, and reduced skin elasticity, and internally by the breakdown of dermal collagen and elastin. Free radicals can be scavenged and the skin can be protected from further oxidative damage by antioxidants. Melatonin is a hormone produced mainly by the pineal gland, as well as many other organs, including the skin. One of the functions of melatonin is exerted by the antioxidative melatoninergic system to prevent ultraviolet (UV)-induced skin photoaging. The aim of this review was to study the protective effect of melatonin on skin photoaging resulting from UVR exposure. The references were tracked using various databases, such as Google Scholar and PubMed with regard to publications in English for the last 5 years (2019-2023). Melatonin inhibits UVR-induced aging in multiple ways, such as protecting skin cells, binding free radicals, accelerating the activity of antioxidant enzymes, preventing increased mitochondrial membrane permeability, and assisting electron transport efficiency in the mitochondrial respiratory chain. Exogenous application of melatonin is usually by the oral route, but for localized effects on the skin, topical administration is recommended, with consideration of preparations with a better half-life and bioavailability. Understanding the protective antioxidant function of melatonin in UV-induced skin photoaging helps to optimize its application. The protective properties of melatonin against UVR-oxidative stress-induced photoaging will be further explored in this review.

SEROTONIN INFLUENCE ON THE CLINICAL COURSE OF PREGNANCY IN THE FIRST TREMESTER

Changes of melatonin and serotonin levels in the plasma can be associated with thedevelopment of the threatened abortion. Hormones of the pineal gland stimulate thesecretion of progesterone, which reduces the contractile activity of the uterus and preventsthe immunological rejection of the trophoblast. The real observations motivated us tostudy serotonin plasma concentrations in cases of the threatened abortion.The aim of the study – to study changes in serotonin levels in pregnant women withclinical manifestations of the threatened abortion before 12 weeks of gestation comparedto women with normal pregnancies.Research material and methods. Two groups were formed: the 1st main group –40 pregnant women with signs of threatened abortion, the 2nd control group – 44 healthypregnant women. An obstetric study, enzyme immunoassay to determine serotonin, andultrasound were carried out. Statistical analysis was conducted according to the generallyaccepted methods of variational statistics.The approval of the scientific work was obtained from the Bioethical Commission of theBukovinian State Medical University (Ukraine).Research results. Results of serotonin levels in venous blood showed their extremeincrease in women with threatened abortion 739.89±111.27 ng/ml compared to normalpregnancy 511.05±140.36 ng/ml (p˂ 0.003). In the pregnant women of the main group,consisting of 40 women, almost all of them had an increased serotonin, except 4 women(10%). This can be explained by hypoprogesteronemia in women with a threat of abortion.Therefore, we consider the change in serotonin concentration as a secondary process thatdoes not require specific treatment. Attention is also drawn to the fact of a reduced levelof serotonin in the control group in cases of further complicated course. Conclusions. Serotonin levels were higher in patients with threatened abortion comparedto uncomplicated pregnancies. Changes in serotonin plasma in cases of threatenedabortion are a consequence, not a cause of abortion, therefore pregnant women needtreatment of obstetric pathology, namely the prescription of progesterone.

Association between nocturnal light exposure and melatonin in humans: a meta-analysis.

Night shift workers are more susceptible to circadian rhythm disturbances due to their prolonged exposure to nighttime light. This exposure during abnormal periods causes inappropriate suppression of melatonin synthesis and secretion in the pineal gland, thereby disrupting circadian rhythms. While it is believed that nocturnal light exposure is involved in suppressing melatonin secretion, research findings in this area have been inconsistent. Thirteen publications retrieved from PubMed and Web of Science databases were included to compare the differences between night shift workers and controls using aggregated mean differences (MD) and 95% confidence intervals (CI). After a comprehensive review, 13 publications were included and data on urinary melatonin metabolite 6-sulfameoxymelatonin(aMT6s) were collected for meta-analysis. The results showed that the morning urinary aMT6s levels were significantly lower in the exposed group than in the non-exposed group (MD = -3.69, 95%CI = (-5.41, -1.98), P < 0.0001), with no significant heterogeneity among the original studies (I2 = 42%, P = 0.13). In addition, night shift workers had significantly lower mean levels of 24-h urinary aMT6s than day shift workers (MD = -3.38, 95%CI = (-4.27, -2.49), P < 0.00001, I2 = 0). Nocturnal light was correlated with nocturnal urine aMT6s secretion and inhibited nocturnal aMT6s secretion (MD = -11.68, 95%CI = (-15.70, -7.67), P < 0.00001, I2 = 0). Additionally, nocturnal light inhibited the secretion of melatonin in the blood, with no significant heterogeneity between studies (MD = -11.37, 95%CI = (-15.41, -7.33), P < 0.00001, I2 = 0). The findings of this study indicate that exposure to nocturnal light among night shift workers leads to inhibition of melatonin secretion.